DESCRIPTION: A new class of efficient, photochemically activated DNA cleaving agents of the general dihydrodioxin (DHD) structure which function as masked cleaving reagents has been developed. Initial studies have demonstrated that these DHD'S effectively nick and cleave DNA photochemically at low concentrations and light intensities using long wavelength UV (365 nm) light. Transient spectroscopic results obtained indicate that the DHD DNA cleaving reagents are photochemically fragmented to form phenanthrenequinone in the DNA matrix. It is the photochemically activated ortho-quinones which then react with the DNA via either a hydrogen abstraction and/or an electron transfer mechanism which leads to cleavage of the DNA. In the proposed research, a variety of DHD'S will be synthesized. Each DHD consists of three units: 1) a Masked Cleaving Unit (MCU, which are the ortho-quinones), 2) a Template Unit (TU), and 3) a Sequence-Recognizing Unit (SRU). Thus, in theory, hundreds of variations of DHD'S could be prepared using a "combinatorial" approach. And, if this building block approach can be implemented, then it should be possible to develop sets of precision molecular components (MCU's, TU's, and SRU's) that can be used in any combination to prepare a wide variety of nucleic acid cleaving reagents. Thus, these DNA cleaving reagents could serve as synthetic restriction enzymes, and could be custom designed for specific applications such as the targeting and destruction of specific organisms and cell types such as HIV or specific types of cancer cells; or, for the simple cleaving of a single strand of DNA or RNA as the first step in a sequence of operations to excise or insert genetic material.